Abstract:
INTRODUCTION:Inhaled corticosteroids are the only drugs that effectively suppress the airway inflammation, but they can induce considerable systemic and adverse effects when they are administered chronically at high doses. Consequently, the pharmaceutical industry is still searching for newer entities with an improved therapeutic index. AREAS COVERED:Herein, the authors review the research in the glucocorticoid field to identify ligands of the glucocorticoid receptor (GR). These ligands preferentially induce transrepression with little or no transactivating activity, in order to have a potent anti-inflammatory action and a low side-effects profile. EXPERT OPINION:Several agents have been synthesized, but few have been tested in experimental models of asthma. Furthermore, only three (BI-54903, GW870086X and AZD5423) have entered clinical development, although the development of at least one of them (BI-54903) was discontinued. The reason for the limited success so far obtained is that the model of transactivation versus transrepression is a too simplistic representation of GR activity. It is difficult to uncouple the therapeutic and harmful effects mediated by GR, but some useful information that might change the current perspective is appearing in the literature. The generation of gene expression 'fingerprints' produced by different GR agonists in target and off-target human tissues could be useful in identifying drug candidates with an improved therapeutic ratio.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Cazzola M,Coppola A,Rogliani P,Matera MGdoi
10.1517/13543784.2015.1078310subject
Has Abstractpub_date
2015-01-01 00:00:00pages
1473-82issue
11eissn
1354-3784issn
1744-7658journal_volume
24pub_type
杂志文章,评审abstract::New therapies targeting critical elements of the cell cycle open novel and attractive avenues for the treatment of cancer patients. At present, the number of clinical trials that are registered with the European Organization for Research and Treatment of Cancer (EORTC) and with the US National Cancer Institute, which ...
journal_title:Expert opinion on investigational drugs
pub_type: 社论
doi:10.1517/13543784.2012.691163
更新日期:2012-08-01 00:00:00
abstract:INTRODUCTION:Recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) has a dismal prognosis. With the emergence of monoclonal antibodies and tyrosine kinase inhibitors (TKI) targeting the epidermal growth factor receptor (EGFR), several drugs were developed and tested in HNSCC. To date, the monoclonal...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2016.1177022
更新日期:2016-06-01 00:00:00
abstract::Zolmitriptan is a new oral acute treatment for migraine. It is a selective and potent agonist at the serotonin (5-HT)(1B/1D) receptor and was developed to improve on the oral bioavailability, tissue selectivity and CNS penetration of earlier compounds. Animal studies confirmed that these objectives had been attained. ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.7.4.633
更新日期:1998-04-01 00:00:00
abstract:INTRODUCTION:Sepsis with Bacillus anthracis infection has a very high mortality rate despite appropriate antibiotic and supportive therapies. Over the past 15 years, recent outbreaks in the US and in Europe, coupled with anthrax's bioterrorism weapon potential, have stimulated efforts to develop adjunctive therapies to...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.1041587
更新日期:2015-01-01 00:00:00
abstract::Gossypol has received significant attention as a result of its potential therapeutic application as a male antifertility agent. Furthermore, recent research examining the biological activity of gossypol has revealed a number of other promising lines of enquiry. These have focused on the antitumour, antiviral and antio...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.14.11.1419
更新日期:2005-11-01 00:00:00
abstract:INTRODUCTION:Epithelial ovarian cancer (EOC) is the fourth commonest cause of female cancer death in the developed world. Although progress in treatment has improved survival, ∼ 80% of patients with advanced EOC will experience a recurrence and eventually will become resistant to chemotherapy. The aim of treatment for ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.1072168
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:Diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) are the two complications of diabetes that cause visual loss and blindness. Laser photo-coagulation in the past was used to prevent progression of disease to these advanced stages. Advances in pathophysiologic understanding of DME an...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2016.1201062
更新日期:2016-09-01 00:00:00
abstract:INTRODUCTION:The addition of monoclonal antibody (mAb) epidermal growth factor receptor (EGFR) inhibitors to classic chemotherapy doublet backbones has improved survival of metastatic colorectal cancer (mCRC). However, the role of triple-drug chemotherapy regimens in combination with an anti-EGFR mAb inhibitor is not y...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2019.1599860
更新日期:2019-05-01 00:00:00
abstract:INTRODUCTION:GLP-1 receptor agonists have been shown to be effective in the treatment of type 2 diabetes mellitus (T2DM). Although the first GLP-1 receptor agonist, exenatide, was approved in the mid-2000s, other agents with longer durations of action (that do not require twice-daily dosing) are now being developed. In...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2012.638282
更新日期:2012-01-01 00:00:00
abstract::Asthma and chronic obstructive pulmonary disease (COPD) are diseases of the airways with an underlying inflammatory component. The prevalence and healthcare burden of asthma and COPD is still rising and is predicted to continue to rise in the current century. The beta-agonists and corticosteroids form the basis of the...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.1.5
更新日期:2003-01-01 00:00:00
abstract:INTRODUCTION:Sorafenib is an oral multikinase inhibitor with anti-angiogenic and anti-proliferative activity that is indicated for use in hepatocellular and renal cell carcinomas. Sorafenib is being developed in a number of solid tumors, including breast cancer (BC). AREAS COVERED:A series of four randomized, double-b...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2012.689824
更新日期:2012-08-01 00:00:00
abstract::Biologically-based skin substitutes have developed as commercial products over the last 5 years. The first generation includes the collagen-based synthetic device, Integra, and Alloderm, which is based on devitalised and cross-linked human dermis. These are used as dermal replacements for third degree burns. Within th...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.7.5.803
更新日期:1998-05-01 00:00:00
abstract:INTRODUCTION:Therapeutic options for mycosis fungoides and Sézary syndrome include a variety of immunomodulatory, epigenetic, and cytotoxic options; however, none has been demonstrated to be efficacious for all patients, or to deliver deep and durable responses to the majority of patients. In this review, we examine th...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2018.1498081
更新日期:2018-08-01 00:00:00
abstract::Psoriasis is a chronic skin disorder characterised by inflammation producing red, thickened areas with a flaky white build-up. Efalizumab is a humanised monoclonal IgG1 antibody that inhibits the binding of T lymphocytes to endothelial cells and their subsequent migration. In patients suffering from plaque psoriasis, ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.13.5.551
更新日期:2004-05-01 00:00:00
abstract::Risperidone (Risperdal) is a benzisoxazole derivative with a high affinity for serotonin 5-HT2 and dopamine D2 receptors, and some affinity for alpha- adrenergic, histamine H1 and dopamine D1 receptors. It has no anticholinergic effects. Early studies demonstrated risperidone to be an effective medication for psychoti...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.8.4.443
更新日期:1999-04-01 00:00:00
abstract::The eating disorders anorexia nervosa, bulimia nervosa and binge eating disorder are common, significant public health problems which are treated with nutritional, psychotherapeutic and pharmacological interventions. A number of drugs (mostly antidepressant drugs) are currently used in their treatment to some benefit,...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.3.491
更新日期:2003-03-01 00:00:00
abstract::INH-A21 is an experimental human immune globulin for intravenous infusion (IGIV) derived from donors specifically selected for elevated levels of antibodies against the Staphylococcal fibrinogen-binding proteins, serine aspartate dipeptide repeat G and clumping factor A. Phase II results demonstrated that infusions of...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.15.6.703
更新日期:2006-06-01 00:00:00
abstract:INTRODUCTION:There has been a striking increase in the emergence of multidrug-resistant pathogens in recent times. Delafloxacin is a novel, broad-spectrum fluoroquinolone with antimicrobial activity against resistant Gram-positive, Gram-negative and anaerobic organisms. It has the potential to treat a variety of infect...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.1005205
更新日期:2015-03-01 00:00:00
abstract::Binding of microbial cell surface adhesins to host receptor molecules is a critical early step in microbial infection and pathogenesis. Anti-adhesive strategies aimed at blocking this interaction offer an attractive means of preventing infection at an early stage. The strategy should reduce the likelihood of resistant...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.8.1711
更新日期:2000-08-01 00:00:00
abstract:INTRODUCTION:Regorafenib (BAY 73-4506) is a novel, orally active, diphenylurea multikinase inhibitor of VEGFR1-3, c-KIT, TIE-2, PDGFR-β, FGFR-1, RET, RAF-1, BRAF and p38 MAP kinase. AREAS COVERED:This review covers the preclinical development of regorafenib as well as the pivotal Phase I studies. The safety profile of...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2012.684752
更新日期:2012-06-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Antibacterial drug discovery and development has slowed considerably in recent years, with novel classes discovered decades ago and regulatory approvals tougher to get. Traditional approaches and the newer genomic mining approaches have not yielded novel classes of antibacterial compounds. Inste...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780903505092
更新日期:2010-02-01 00:00:00
abstract::AGI-1067 is a derivative of probucol that is a promising new development for the treatment of restenosis and possibly atherosclerosis. In monkeys fed a high-fat diet for 1 year, AGI-1067 prevented the development of atherosclerosis. In these monkeys, AGI-1067 lowered plasma levels of low-density lipoprotein (LDL)-chol...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.11.1855
更新日期:2003-11-01 00:00:00
abstract:INTRODUCTION:The Philadelphia chromosome negative myeloproliferative neoplasms (MPN) mainly comprise polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF, primary or post-PV/ET). Therapy in PV and ET focuses on minimizing thrombosis and bleeding risk, while in MF, prolongation of survival is an ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2016.1250882
更新日期:2016-12-01 00:00:00
abstract::Introduction: Neuropathic pain is a chronic condition that significantly affects the quality of life of millions of people globally. Most of the pharmacologic treatments currently in use demonstrate modest efficacy and over half of all patients do not respond to medical management. Hence, there is a need for new, effi...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2020.1728254
更新日期:2020-03-01 00:00:00
abstract:INTRODUCTION:Cardiovascular disease is the leading cause of death worldwide, accounting for 30% of all deaths, with elevated blood pressure probably the most important modifiable risk factor. Worldwide, elevated blood pressure is estimated to cause 7.5 million deaths, about 12.8% of the total of all annual deaths. New ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2013.797962
更新日期:2013-07-01 00:00:00
abstract:INTRODUCTION:Soft tissue sarcomas (STS) are a rare and difficult to treat malignancy. Efforts to utilize targeted therapy have been ongoing for the last decade and have resulted in the approval of pazopanib for treatment of advanced disease. Although several other agents have been investigated, the inability to predict...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.1076792
更新日期:2015-01-01 00:00:00
abstract::The beneficial effect of beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in primary prevention of coronary artery disease in those with hypercholesterolaemia and in secondary prevention in those with established coronary vascular disease are now well known. A growing body of eviden...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.10.10.1847
更新日期:2001-10-01 00:00:00
abstract::It is now widely accepted that the renin-angiotensin system (RAS) not only contributes to pathological mechanisms involved, e.g. in hypertension or hypertensive and diabetic end-organ damage, but also harbors a "protective arm" represented mainly by two receptors, the AT2 (angiotensin type 2) receptor and the Mas rece...
journal_title:Expert opinion on investigational drugs
pub_type: 评论,杂志文章
doi:10.1517/13543784.2012.681046
更新日期:2012-06-01 00:00:00
abstract::TNP-470, an analogue of fumagillin, has been shown to inhibit angiogenesis in vitro and in vivo. In 1992, TNP-470 entered clinical development for cancer as an anti-angiogenic agent. It is currently in Phase I/II trials in Kaposi's sarcoma, renal cell carcinoma, brain cancer, breast cancer, cervical cancer and prostat...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.6.1383
更新日期:2000-06-01 00:00:00
abstract:BACKGROUND:Pompholyx is a chronic relapsing inflammatory vesicobullous skin disease of the hands and feet belonging to the spectrum of eczema. Established treatments, both topical and systemic, are limited in efficacy, risk:benefit ratio and prevention of further relapses. New treatment options are needed. OBJECTIVE:T...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.17.6.897
更新日期:2008-06-01 00:00:00